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 Research & Giving News Article  Imaging study led by NARSAD Young Investigator is one of first to analyze influence of multiple genes "Schizophrenia is a highly genetic disorder, but we are learning that its genetics are not straightforward,” said NARSAD Young Investigator Joshua Roffman, M.D., director of Mass General’s Schizophrenia Clinical and Research Program and the study’s lead author. “In most cases, potential risk genes appear to have very small effects on symptoms, making it difficult to attribute clinical findings to particular genes. To amplify some of these subtle effects, we and others are looking at how the genes affect brain function, rather than just behavior." Dr. Roffman’s team, which included investigators from the University of New Mexico, University of Iowa and University of Minnesota through the MIND Clinical Imaging Consortium, used functional MRI to scan an area of the prefrontal cortex known to be critical to working memory in 79 schizophrenia patients and 75 healthy controls as they completed a memory task. Levels of cortical activity were then analyzed for association with common variants in two genes: MTHFR, which regulates folate metabolism and has been associated with schizophrenia risk, and COMT, involved with dopamine processing during working memory. The schizophrenia-associated variant of MTHFR was found in both patients and controls, but when the memory task became more difficult, weaker cortical function associated with that variant was seen only in the schizophrenia patients. While variations in COMT by themselves did not influence cortical activation patterns, the combined effects of both genes did. The reduction in cortical function seen in patients with the schizophrenia-associated MTHFR variant was even more pronounced in patients who also had a COMT variant previously associated with less efficient working-memory-related brain activity. ”These findings may help us to identify patients more likely to benefit from new treatments targeting the dopamine and folate systems," Dr. Roffman stated. "We are hopeful that this approach will catalyze the development of individualized treatment regimens, since it will allow us to examine the effects of treatment-related genes on brain function using a much smaller group of study participants. (This news article was adapted with permission from Massachusetts General Hospital.) |
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